Dendritic cells (DCs) are the most powerful antigen presenting cells in the living body. Dendritic cells are known to induce immune responses by presenting antibodies to T cells. In addition, it is also known that DCs play a central role in immune reactions by directly acting not only on T cells but also on B cells, NK cells, NKT cells, and the like. Immature DCs receive antigen stimulation so as to cause an increase in the expression of CD40, CD80, CD86, or the like. Accordingly, DCs attain T cell stimulatory capacity. In addition, DCs migrate to peripheral lymphatic tissue and activate T cells that are specific to antigens incorporated thereinto so as to induce immune responses.
In general, there are only a small number of references that disclose substances recognized as having the ability to induce dendritic cell(-like) differentiation from blood precursor cells. Most such substances are well-known cytokines. For instance, there are many reports on the induction of differentiation caused by the combined use of GM-CSF and IL-4. This combination is called a “gold standard” for dendritic cell differentiation. In addition, as substances capable of inducing dendritic cell differentiation when used alone or in combination, TNF-alpha, IL-2, IL-3, IL-6, IL-7, IL-12, IL-13, IL-15, HGF (hepatocyte growth factor), a CD40 ligand, M-CSF, an Flt3 ligand, and TGF-beta have been reported. Among these proteins, examples of a substance capable of inducing precursor cells to differentiate into dendritic cell(-like) cells when used alone include IL-2, IL-15, HGF, and a CD40 ligand. Of these, only IL-2 has been confirmed to have in vivo anticancer effects (see Non-Patent Document 1).
Meanwhile, the REIC gene is known as a gene involved in cell immortalization. It has been reported that the expression of the gene is suppressed in cancer cells (see Patent Document 1 and Non-Patent Documents 2 to 5).
The REIC gene is a member of the Dkk family. It has been suggested that Dkk-1, which is a member of such family, inhibits Wnt signal transduction via Wnt receptors (Non-Patent Documents 6 and 7). The Wnt gene has been reported to play multifaceted roles in important biological phenomena such as cell growth, cell differentiation, and canceration (see Non-Patent Document 8). Therefore, similarly, the Dkk family (including 4 currently known human genes) probably has important functions for cell growth, cell differentiation, and canceration. However, most of the functions of the Dkk family have not been elucidated.
Patent Document 1: WO01/038523
    Non-Patent Document 1: Zou G M. Et al., Eur Cytokine Netw. 2002 April-June; 13(2):186-99.    Non-Patent Document 2: Tsuji, T. et al., BiochemBiophys Res Commun 268, 20-4 (2000)    Non-Patent Document 3: Tsuji, T. et al., BiochemBiophys Res Commun 289, 257-63 (2001)    Non-Patent Document 4: Nozaki, I. et al., Int J Oncol 19, 117-21 (2001)    Non-Patent Document 5: Kurose, K. et al., J Urol 171, 1314-8 (2004)    Non-Patent Document 6: Bafico, A. et al., Nat Cell Biol 3, 683-6 (2001)    Non-Patent Document 7: Hoang, B. H. et al., Cancer Res 64, 2734-9 (2004)    Non-Patent Document 8: Moon, R. T. et al., Science 296, 1644-6 (2002)